When cells age and stop dividing, that’s called cellular senescence. In the short term, senescence protects against DNA damage and tumor formation. Then the immune system eliminates the senescent cells.

As we age, however, senescent cells don’t get eliminated. Their buildup in the body has long been considered problematic, contributing to inflammation and age-related diseases. Scientists have even found that getting rid of senescent cells in mice extends their lifespan.

However, new research indicates that senescence is essential for the regeneration of heart tissue. 

This is the surprising conclusion of a Weizmann Institute of Science study published in Nature Cardiovascular Research by a research team led by Dr. Rachel Sarig and student Lingling Zhang from the cardiac healing and regeneration research laboratory of Prof. Eldad Tzahor. 

The scientists have revealed in unprecedented detail – at the level of individual cardiac fibroblast cells – how senescence is activated briefly following injury to the heart muscle of mice, serving as a vital part of the heart’s healing process. 

Senescent cells displayed enhanced activation of signaling pathways associated with tissue repair and regeneration in two mouse models of cardiac injury that exhibit robust senescence.

Don’t get rid of them

Their findings are part of an accumulating group of studies showing a critical role for transient senescence in various developmental and regenerative models. 

“Senescence is usually associated with aging and disease. We hypothesized that regeneration, which is facilitated by cell division, would be negatively associated with senescence levels that indicate cell cycle arrest. Surprisingly, during the initial few days of cardiac regeneration in mice we saw increased, rather than decreased, senescence levels,” Sarig and Tzahor report. 

“This paradox was resolved by two major observations — the fact that the robust senescence was transient and completely disappeared within three weeks, and by the identification of cardiac fibroblasts as the major targets of regenerative senescence, rather than cardiomyocytes.”

Therefore, simply getting rid of all senescent cells could be the wrong approach.

“Numerous studies across different organs and disease models, including aging and models of heart diseases, have explored the prospect of eliminating senescent cells in order to enhance tissue function,” the scientists write. 

“Our study, alongside previous research demonstrating essential beneficial roles for senescent cells, underscores the need for caution when attempting to non-specifically remove these cells using various drugs, as such interventions could be detrimental if applied during the healing process.”

More to understand

Sarig and Tzahor added that at this time, “the molecular mechanisms that control cardiac fibroblast senescence and its potential benefits for cardiac repair remain poorly understood,” and they intend to do further studies.

“It will be interesting to explore the similarities and discrepancies between regenerative senescent cells and those in disease and aging models. A key question for further investigation is whether these cells express different factors or if the senescence-associated secretory phenotype [SASP] components are similar, with the primary difference being their kinetics.”

They hypothesize that transient SASP expression is beneficial for regeneration, whereas persistence expression is detrimental. 

“Despite a growing number of studies showing the positive aspects of senescence, the common view in the field remains that senescence is deleterious for human health. We hope that our study serves to change that view.”